PEDIATRICS (ISSN 0031 4005). Copyright © 1985 by the American Academy of Pediatrics.
Metabolic
Aspects
of Phototherapy
Paul
Y.
K.
Wu,
MD,
Joan
E.
Hodgman,
MD,
Barry
V.
Kirkpatrick,
MD,
Nathaniel
B. White,
Jr,
M Phil,
and
Dolores
A.
Bryla,
MPH
From the Department of Pediatrics, University of Southern California School of Medicine,
LAC/USC Medical Center, Los Angeles; Department of Pediatrics, Medical College of
Virginia, Virginia Commonwealth University, Richmond, and Biometry Branch,
Epidemiology and Biometry Research Program, Nationallnstitute of Child Health and
Human Development, National Institutes of Health, Bethesda, Maryland
Recent
studies have shown that exposure tonon-ionizing radiant energy may induce physical and metabolic effects in the neonate. The effects include changes in body temperature37”#{176}5”#{176};- peripheral blood flow75”05”08; insensible water 10557576105; gas trointestinal (GI) tract motility; and nutrient, elec-trolyte, and water balances.4’76’’89”#{176} In an effort to evaluate the influence of intake of fluid and calories on neonatal jaundice and the efficacy of photother-apy, the metabolic data obtained from the National Institute of Child Health and Human Development
(NICHD) phototherapy study were analyzed. The results constitute the subject of this report.
MATERIALS
AND
METHODS
The data were collected from 1,339 infants en-rolled in the study from the six participating insti-tutions as described by Bryla.’8
Fluid
Intake
To determine whether the daily total fluid intake might affect total serum bilirubin levels, the data
were analyzed by dividing the control and photo-therapy-treated infants in each weight group into four subgroups according to their total daily intake. The subgroups are: A, <60 mL/kg/24 hours; B, 60 to 89 mL/kg/24 hours; C, 90 to 119 mL/kg/24 hours; and D, 120 mL/kg/24 hours.
The amount of total fluid intake used for char-acterization of the subgroups was determined
mi-tially by plotting all daily total intakes against total serum bilirubin levels for the corresponding day in a scattergram. The trend in clusters observed in thescattergram was then used to designate the
amounts in the four subgroups.
Caloric Intake
To determine whether the mean daily total ca-loric intake might affect total serum bilirubin levels, the data were analyzed by separating the control and phototherapy-treated infants in each birth
weight group into three subgroups according to
their mean daily total caloric intake during the phototherapy period. The subgroups are: A, <60
calories/kg/24 hours; B, 60 to 90 calories/kg/24 hours; and C, >90 calories/kg/24 hours.
Additionally, the data were further analyzed ac-cording to intravenous and oral caloric intake sep-arately using the same three caloric subgroups (A, B, and C listed above).
Statistical
Analysis
Daily means for the phototherapy and control groups were compared using the t test for unpaired data. For comparison of subgroups (eg, fluids sub-groups A to D, and calories subgroups A to C), the analysis of variance procedure was used to compare the mean values of the variables (eg, total bilirubin
level, z bilirubin, 2-(4-hydroxyazobenzene)benzoic acid [HBABAJ binding).
RESULTS
Group
I (Birth
Weight
Less
Than
2,000
Grams)
TABLE 1.
Than 2,000
Relation of Daily Mean Total Serum Bilirubin Level to Fluid Intake for Infants
Grams, by Phototherapy (P) and Control (C) Groups*
with Birth Weight Less
Hours Into Study
Meati Total Serum Bilirubin Level (mg/dL)
Subgroup A Subgroup B Subgroup C
(<60 mL/kg/24 h) (60-89 mL/kg/24 h) (90-119 mL/kg/24 h)
Subgroup D (120 mL/kg/24 h)
P C P C P C P C
0 24 48 72 96 120 144
6.0 ± 1.9 5.4 ± 1.5#{176}5.7 ± 1.9 5.8 ± 2.4 5.9 ± 1.8 5.5 ± 1.8
6.8 ± 2 7.8 ± 1.6 6.5 ± 2.1” 8.3 ± 2.9” 6.0 ± 2.O’ 8.0 ± 2.5”
8.1 ± 2.5 10.6 ± 4.0 6.3 ± 2.1” 10.1 ± 3.1” 6.4 ± 2.8” 9.6 ± 3.3”
6.9 ± 3.2#{176} 12.9 ± 6.9#{176}7.1 ± 2.9” 11.4 ± 3.1” 6.2 ± 2#{149}6b 10.6 ± 3.3”
8.4 ± 5.3 9.4 ± 0.4 7.7 ± 2.4” 10.8 ± 3.4” 5.8 ± 2#{149}9b 10.9 ± 3.4”
7.7 ± 4.3 10.3 ± 2.1 9.0 ± 4.2 10.5 ± 5.1 7.3 ± 3.5” 10.8 ± 3.3”
7.6 ± 4.1 10.4 ± 5.1 7.2 ± 31b 9.2 ± 3.8”
5.7 ± 1.9 5.5 ± 2.1
6.3 ± 2.3k 75 2.6”
6.3 ± 2.4” 9.3 ± 3.2” 5.9 ± 2.6” 9.5 ± 3#{149}5b 5.5 ± 2.5” 9.1 ± 3.6” 5.9 ± 2.6” 8.3 ± 3.4” 6.1 ± 2#{149}9b 7.6 ± 34b * Values are means ± SD. Significance is indicated as follows:
a, P
< .05;b, P
< .01. Blank spaces indicate that there were no infants in that fluid intake group for that day.TABLE 2. Relation of Daily Mean Total Serum Bilirubin Level to Oral Caloric Intake
for Infants with Birth Weight Less Than 2,000 Grams, by Phototherapy (P) and Control
(C) Groups*
Hours Into Subgroup A Subgroup B Subgroup C
Study (<60 Calories/kg/24 h) (60-90 Calories/kg/24 h) (>90 Calories/kg/24 h)
P C P C P C
0 5.8 ± 1.8 5.6 ± 1.8 6.1 ± 2.2 5.6 ± 2.6 5.5 ± 1.6 5.5 ± 2.3
24 6.4 ± 2.0” 8.0 ± 2.6” 6.3 ± 2.3” 8.1 ± 26b 59 23b 7o 2.8”
48 6.7 ± 2.5” 10.0 ± 33b 6.3 ± 2.7” 9.8 ± 2.9” 6.0 ± 2.2” 8.5 ± 3.3”
72 6.3 ± 2.6” 10.6 ± 34b 6.4 ± 2.9” 10.5 ± 3.2” 5.7 ± 2.4” 8.8 ± 3.6”
96 6.6 ± 3.1” 10.9 ± 3.6” 5.6 ± 25b 10.3 ± 3.2” 5.2 ± 2.3” 8.4 ± 36b
120 7.7 ± 3.6” 11.1 ± 3.6” 6.7 ± 3#{149}0b 9.2 ± 3.3” 5.6 ± 2.4” 7.7 ± 3.4”
144 7.9 ± 3.6” 10.3 ± 3.9” 6.9 ± 3.2” 8.6 ± 3.7” 5.8 ± 26b 7o 3#{149}0b
* Values are means ± SD. Significance is indicated as follows:
b, P
< .01.428 PHOTOTHERAPY FOR NEONATAL HYPERBILIRUBINEMIA
serum bilirubin level was similar in both control
and phototherapy-treated infants, with the excep-tion of the third day of phototherapy, when mean serum bilirubin level was lower in the photother-apy-treated infants. In all the subgroups with
higher fluid intake (B, C, D), the daily mean serum bilirubin level was significantly lower in the
pho-totherapy-treated infants during the phototherapy period compared with values in control infants
(P
< .01). During the postphototherapy period, the
daily mean serum bilirubin level was lower
(repre-senting lower rebound) in subgroups C and D in
the treated infants
(P
< .01).There was a strong tendency for higher fluid intakes to be associated with lower daily serum bilirubin levels, in both phototherapy and control groups. However, the differences did not reach sta-tistical significance (Table 1).
Bilirubin
and
Caloric
Intake.
The relationship of the three caloric intake subgroups to daily meantotal serum bilirubin level is shown in Table 2. As expected, phototherapy-treated infants had signifi-cantly lower daily mean serum bilirubin
concentra-tions than control infants in all caloric subgroups. Higher caloric intake was associated with lower
serum bilirubin level in both control and
photo-therapy-treated infants based on Duncan’s multiple
range test. The effect of increased caloric intake on the lowering of mean serum bilirubin level was greater in the control infants than in the photo-therapy-treated infants.
In the immediately postphototherapy period (48
hours), control infants showed a continued steady
decrement in mean serum bilirubin level in all
caloric subgroups. Most phototherapy-treated
in-fants showed a rebound. The magnitude of the
rebound in serum bilirubin level was greater in infants with lower caloric intake than in infants with higher caloric intake.
To determine whether the observed differences in serum bilirubin levels associated with the differ-ent caloric intake subgroups were related to the route of caloric intake, the data were analyzed separately according to intravenous and oral caloric intake. Although there was a trend for higher intra-venous caloric intakes to be associated with lower serum bilirubin levels, the differences were not
statistically significant.
When the mean daily serum bilirubin was
ana-lyzed according to oral caloric intake subgroups, serum bilirubin was found to be inversely correlated to oral caloric intake in both phototherapy-treated
and control infants (Figure). The differences in mean serum bilirubin level between the caloric
at Viet Nam:AAP Sponsored on September 7, 2020
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11 r
10
9
8
D)
E
z
-I
w U)
-I
I-0
I-z
Ui 7
6
5
4
LIGHTS OFF
1 I L I I
24 48 72 96 120 144
* Values are means ± SD. Significance is indicated as follows:
b, P
< .01. groups were more pronounced in control infants.Interestingly, the mean serum bilirubin level in the infants in control group C (>90 calories/kg/24 h) was similar to the mean serum bilirubin level in
CAL/kg/24hr. A. <60
p
.- - --. CONTROL
B. 60-90
A -i PHOTOTHERAPY
#{163}-- - -a CONTROL C. >90
p p PHOTOTHERAPY
.-- --U CONTROL
HOURS ON STUDY
Figure.
Mean
changes (±SE) in daily serum bilirubin level relative to three oral caloric intake subgroups (A, B, and C). Note greater lowering of mean serum bilirubin level in subgroup C from subgroups A and B of controlinfants compared with subgroup C from subgroups A and
B of phototherapy-treated infants.
phototherapy group A (<60 calories/kg/24 h) on the first and fifth day, and was significantly lower
on the sixth day of the study.
The relative decrement in bilirubin in photother-apy-treated infants was greatest in the first 24 hours, and the extent of decrement was directly
related to caloric intake. At the termination of phototherapy, the bilirubin level in the treated in-fants rebounded in all caloric subgroups. Higher
caloric intake was associated with a lower rebound in serum bilirubin (Table 2).
The mean peak serum bilirubin level was higher in control than in light-treated infants in all oral caloric subgroups
(P
< .01). Higher oral caloric intake was associated with lower peak bilirubin levels (Table 3). Thus, control subgroup C had significantly lower peak bilirubin level than sub-groups A and B(P
< .05) and phototherapy sub-groups B and C had significantly lower peak bili-rubin level than subgroup A.Although the day of peak serum bilirubin level occurred later in control than in light-treated in-fants (Table 4), the differences were only
signifi-cant between the subgroups with the highest caloric intake (C)
(P
< .05). The day of peak serum bili-rubin level was significantly earlier in subgroups B and C than subgroup A for both control and pho-totherapy-treated infants in the weight groups, 2,000 to 2,499 g and 2,500 g or more. However, inthe group with birth weight less than 2,000 g, only the phototherapy group with the highest caloric
intake (C) was significantly different from the low-est caloric group (A).
Stools.
During the phototherapy period, light-treated infants passed stools more frequently than control infants in all caloric intake subgroups (Ta-ble 5). During the postphototherapy period, thefrequency of stools was comparable in photother-apy-treated and control infants. In general, higher caloric intake was associated with more frequent
TABLE
First Fo
3. Relat
ur Days o
ion of Peak Serum Bilirubin Level to Average Oral Caloric Intake During f Study by Birth Weight, by Phototherapy (P) and Control (C) Groups*
Mean Peak Serum Bilirubin Level (mg/dL)
Birth Weight Birth Weight Birth Weight
<2,000 g 2,000-2,499 g 2,500 g
P C P C P C
Subgroup A
(<60 calories/ 8.4 ± 30b 11.7 ± 36b 14.4 ± 3.4 16.6 ± 4.4 15.4 ± 2.2” 18.0 ± 1.6”
kg/24 h)
Subgroup B
(60-90 calories/ 7.9 ± 2.5” n ± 3.1” 12.8 ± 1.6” 14.8 ± 2.8” 15.7 ± 2.5” 17.2 ± 2.5” kg/24 h)
Subgroup C
*
Values
are means
±SD.
430
PHOTOTHERAPY
FOR
NEONATAL
HYPERBILIRUBINEMIA
TABLE 4.
Relation
of Day of Peak
Serum
Bilirubin
Level
to Average
Oral Caloric
Intake
During
First
Four
Days
of Study
by Birth
Weight,
by Phototherapy
(P) and
Control
(C)
Groups*
B irth Weight <2,000 g
Birth Weight 2,000-2,499 g
Bi rth Weight 2,500 g,
P C P C P C
Subgroup
A
(<60
calories/kg/24
h)
4.1 ± 2.3 4.1 ± 1.6 3.1 ± 2.4 3.5 ± 1.0 1.6 ± 0.8 2.5 ± 0.8Subgroup
B
(60-90
calories/kg/
3.7
± 2.3 3.9 ± 1.3 1.2 ± 0.4” 3.0 ± 1.3” 1.3 ± 0.7” 1.8 ± 1.0”24 h)
Subgroup
C
(>90
calories/kg/24
h)
2.9
± 1#{149}9b39
1#{149}6b1.3 ± 0.7” 2.0 ± 10b 1.2 ± 0.5” 1.6 ± 0.7” *Values
are means
±SD. Significance
is indicated
as follows:
a, P
<.05; b, P
<.01.
TABLE
5.
Daily
Number
of
Stools
for
Infants
with
Birth
Weight
Less
Than
2,000
Grams,
by Phototherapy
and Control
Groups*
Hours Into Study
Phototherapy Group
Control Group
P
Value
0
3.3
±2.1
2.4
± 0.7 <.0124
3.8
± 1.7 2.7 ± 0.8 <.0148
3.9
± 1.1 2.9 ± 0.8 <.0172 3.6 ± 1.0 2.9 ± 0.8 <.01
96
3.3
±0.9
2.7 ± 0.8 <.01120
3.1
± 0.8 2.9 ± 0.8 NS144
3.2
± 0.7 2.9 ± 0.7 NSstools
in
both
phototherapy-treated
and
control
infants.
This
change
in frequency
with
higher
total
caloric
intake
was
entirely
associated
with
in-creased
oral
caloric
intake
as
use
of
intravenous
caloric
intake
had
no effect
on stool
frequency.
Body
Weight.
There
was
a strong
trend
for
light-treated
infants
to lose
more
weight
during
the
pho-totherapy
period
than
control
infants
during
the
corresponding
days.
During
the
postphototherapy
period,
light-treated
infants
gained
more
weight
than
control
infants.
The
same
trends
were
ob-served
when
the
data
were
analyzed
with
respect
to
oral
caloric
intake
using
Duncan’s
multiple
range
test.
Overall,
higher
oral
caloric
intake
was
associ-ated
with
decreased
weight
loss
or increased
weight
gain.
Group 2 (Birth Weight
2,000 to 2,499 Grams)
and
Group 3 (Birth Weight
2,500 Grams
or More)
Bilirubin
and
Fluid
Intake.
No
significant
differ-ences
in
daily
mean
serum
bilirubin
level
were
observed
between
control
and
phototherapy-treated
infants
in
the
two
lower
fluid
intake
subgroups.
However,
in infants
in the
two
higher
fluid
intake
subgroups,
the
same
trend
as found
in infants
with
birth
weight
ofless
than
2,000
g was
observed:
light-treated
infants
were
found
to have
statistically
sig-nificant
lower
daily
mean
serum
bilirubin
concen-tration
than
control
infants.
Higher
fluid
intakes
were
generally
associated
with
lower
serum
biliru-bin
levels
in both
phototherapy-treated
andcontrol
infants
(Tables
6 and
7). Mean
peak
bilirubin
level
and
dayof peak
were
not
related
to fluid
intake.
Bilirubin
and
Caloric
Intake.
In
all
caloric
sub-groups
in
these
weight
groups,
phototherapy-treated
infants
had
lower
mean
daily
serum
biliru-bin
than
control
infants
(Tables
8 and
9).
The
association
of
lower
serum
bilirubin
with
higher
caloric
intake
was
less
evident
than
in the
infants
in the
group
weighing
less
than
2,000
g. Significant
differences
in mean
daily
serum
bilirubin
level
were
only
observed
between
infants
in caloric
subgroups
A and
those
in subgroups
B and
C. In
contrast
to
infants
who
weighed
less
than
2,000
g, the
impact
of higher
caloric
intake
on lowering
serum
bilirubin
level
was
similar
in phototherapy-treated
and
con-trol
infants.
In
addition,
there
was
no
significant
rebound
in serum
bilirubin
level
following
cessation
of phototherapy.
Although
there
was
a strong
tend-ency
for
the
height
of peak
serumbilirubin
level
and
dayof peak
to
correlate
inversely
with
totalcaloric
intake,
significant
differences
were
found
only
between
subgroup
A and
subgroups
B and
C
(Tables
3 and
4).
When
the
relationship
of oral
caloric
intake
to
daily
mean
serum
bilirubin
level
in the
three
caloric
subgroups
was
examined,
no
significant
difference
in
serum
bilirubin
level
was
found
in association
with
different
oral
caloric
intakes.
Peak
serum
bil-irubin
level
and
day
of peak
were
also
similar
be-tween
the
three
oral
caloric
intake
subgroups.
Stools.
Light-treated
infants
tended
to pass
more
stools
during
the
phototherapy
period.
In the
period
after
phototherapy,
the
frequency
of
stools
was
comparable
in light-treated
and
control
infants.
In
contrast
to
group
1 infants,
there
was
no
relation
between
frequency
of stools
and
level
of peak
bili-rubin
or day
of peak,
probably
because
most
of the
infants
in this
group
entered
the
study
at their
peak
bilirubin
level.
at Viet Nam:AAP Sponsored on September 7, 2020
www.aappublications.org/news
TABLE
6.
Relation of Daily Mean Total Serum Bilirubin Level to Fluid Intake for Infants with Birth Weight of2,000
to 2,499
Grams,
by Phototherapy
(P) and
Control
(C) Groups*
Hours Into Study
Subgroup A (<60 mL/kg/24 h)
P C
Subgroup B (60-89 mL/kg/24 h)
Subgroup C (90-119 mL/kg/24 h)
Subgroup D (120 mL/kg/24 h)
P C P C P C
0 24 48 72 96 120 144
14.0 5.7
12.5 ± 0.3 11.2
12.7 ± 2.1 13.2 ± 2.9 13.9 ± 5.7 12.7 ± 2.6 13.1 ± 1.9 12.2 ± 2.4
13.9 14.9 ± 4.2
6.6 ± 0.7 10.0 ± 1.4
11.8 ± 1.8 12.1 ± 1.5
11.3 ± 2.7” 14.1 ± 2.6” 10.1 ± 3.5” 15.5 ± 3#{149}8b
8.0 ± 2.4” 13.7 ± 3.7”
8.1 ± 3.6 9.9 ± 2.2
6.3 ± 1.5 9.2 ± 3.1
12.3 ± 1.8 12.8 ± 2.2
10.3 ± 2.1” 13.0 ± 24b 8.6 ± 2.9” 13.3 ± 2.8” 7.5 ± 2.4” 11.8 ± 2.9” 6.6 ± 2.3” 10.9 ± 6.6”
6.6 ± 2.4” 9.8 ± 2.9”
6.7 ± 7.0” 8.7 ± 2.6b
*
Values
are means
±SD. Significance
is indicated
by: b, P
< .01. Blank spaces indicate that there were no infants inthat
fluid
intake
group
for that
day.
TABLE 7.
Relation
of Daily
Mean
Total
Serum
Bilirubin
Level
to Fluid
Intake
for Infants
with
Birth
Weight
of
2,500
Grams
or More,
by Phototherapy
(P) and Control
(C) Groups*
Hours Into Study
Subgroup A (<60 mL/kg/24 h)
Subgroup B (60-89 mL/kg/24 h)
Subgroup C (90-119 mL/kg/24 h)
Subgroup D (120 mL/kg/24 h)
P C P C P C P C
0 15.0 ± 2.0 16.0 ± 0.9 15.5 ± 2.7 16.1 ± 2.3 15.9 ± 2.7 15.4 ± 2.8 16.0 ± 2.4 15.6 ± 2.1
24 13.8 ± 1.1 12.2 14.0 ± 2.7#{176}17.2 ± 3.2a 13.2 ± 2.8” 15.1 ± 2.6” 13.5 ± 2.6” 15.0 ± 2.8b
48 13.7 ± 4.1 12.4 ± 4.2 11.6 ± 2.7” 14.2 ± 1.7” 10.8 ± 2.8” 13.2 ± 3.1”
72 8.8 ± 3.4#{176}13.0 ± 3.2#{176}9.1 ± 2.9” 11.8 ± 3.3”
96 6.0 ± 2.8 12.1 7.7 ± 2.9 11.0 ± 2.9 7.8 ± 2.6” 10.2 ± 3.4”
120 9.0 ± 0.7 7.8 ± 3.9 7.3 ± 2.6” 8.6 ± 3.3”
144 6.2 ± 3.2 7.5 ± 0.9 7.5 ± 2.2 7.7 ± 3.3
* Values are means ± SD. Significance is indicated by:
a, P
< .05;b, P
< .01. Blank spaces indicate that there were no infants in that fluid group for that day.TABLE
8.
Relation
of Daily
Mean
Total
Serum
Bilirubin
Level
to Oral Caloric
Inta
of 2,000
to 2,499
Grams,
by Phototherapy
(P) and Control
(C) Groups*
ke for Infants
with
Birth
Weight
Hours Into Subgroup A Subgroup B
Study (<60 Calories/kg/24 h) (60-90 Calories/kg/24 h)
Subgroup C (>90 Calories/kg/24 h)
P C
P C P C
0 12.3 ± 2.0 12.0 ± 2.6 12.6 ± 1.8 13.1 ± 2.1
24 12.0 ± 3.4 13.3 ± 3.4 10.9 ± 1#{149}6b 13.5 ± 1.8”
48
11.1
±4.1
14.4 ± 3.6 9.4 ± 2.6” 13.7 ± 2.8”72 9.4 ± 3.6 13.5 ± 3.4 7.0 ± 2.2” 13.3 ± 40b
96
8.8
± 4.1 9.9 ± 3.4 6.8 ± 2.5 11.4 ± 2.4120 6.4 ± 1.7 10.5 ± 2.9
144 8.7 9.3 ± 2.0 7.2 ± 3.7 10.0 ± 2.3
11.9 ± 1.8 12.4 ± 1.8
10.1 ± 2.4” 13.0 ± 2#{149}6b
8.5 ± 19b 13.3 ± 3.Ob
7.6 ± 2.4” 11.6 ± 2.6”
6.6 ± 2.3” 10.6 ± 3.0”
6.5 ± 2.5” 9.6 ± 2#{149}9b
6.4 ± 2.3b 8.5 ± 2.6”
*
Values
are means
±SD. Significance
is indicated
by: b, P
< .01. Blank spaces indicate that there were no infants inthat
fluid
intake
group
for that
day.
TABLE
9.
Relation
of Daily
Mean
Total
Serum
Bilirubin
Level
to Oral Caloric
Inta
2,500 Grams, by Phototherapy (P) and Control (C) Groups*ke for Infants
with
Birth
Weight
Hours Into Subgroup A Subgroup B
Study (<60 Calories/kg/24 h) (60-90 Calories/kg/24 h)
Subgroup C (>90 Calories/kg/24 h)
P C P C P C
0 15.3 ± 2.5 15.9 ± 2.1 15.9 ± 2.2 15.6 ± 2.7
24 13.3 ± 2.8” 17.2 ± 2#{149}8b 13.6 ± 2#{149}6b 15.1 ± 2.8”
48 10.8 ± 4.1 13.5 ± 3.8 11.3 ± 2.8” 14.0 ± 2#{149}8b
72 8.0 ± 3.8 13.2 ± 3.0 8.8 ± 3.3” 12.1 ± 3.6”
96 6.1 ± 2.0 14.5 ± 3.3 7.5 ± 2.8b 10.9 ±
3.0”
120 8.8 ± 0.0 10.4 ± 0.0 7.4 ± 2.3 8.0 ± 3.9
144 7.4 ± 3.8 6.6 ± 0.0 6.9 ± 2.3 8.0 ± 2.9
16.3 ± 2.2 15.6 ± 2.1
13.4 ± 2.5” 14.7 ± 2#{149}7b
10.8 ± 2.7” 13.0 ± 3.0”
9.2 ± 2.8” 11.7 ± 3.2”
7.9
± 2.5” 10.0 ± 3.4”7.3 ± 3.3” 8.6 ± 3.3”
7.6 ± 2.3 7.7 ± 3.3
* References 6, 27, 28, 35, 42, 77, 93, 103, 107.
432
PHOTOTHERAPY
FOR
NEONATAL
HYPERBILIRUBINEMIA
Body
Weight.
Light-treated
infants
tended
to lose
more
weight
during
the
first
two
days
of
photother-apy
than
control
infants.
However,
the
trend
in
weight
change
was
less
consistent
than
with
group
1
infants.
Again,
this
may
be due
to
the
fact
that
infants in
this
group
were
more
mature
and
entered
the
study
at the
third
or fourth
postnatal
day
when
many
of them
would
already
have
started
to gain
weight.
DISCUSSION
The
data
from
this
study
indicate
that
higher
fluid
intake
tended
to
be
associated
with
lower
serum
bilirubin
levels
in
both
control
and
light-treated
infants.
Conceivably,
good
hydration
may
lower
serum
bilirubin
concentration
by dilution,
but
this
minimal
effect
cannot
explain
the
magnitude
of the
changes.
It
is also
possible
that
increased
fluid
intake
may
improve
blood
flow
and
urinary
secretion
by
improving
water
balance,
leading
to
excretion
of water-soluble
bilirubin
fractions.
Stud-ies
by
Edgren
and
Wester26
have
shown
that
the
glomerular
filtration
rate
is decreased
during
fast-ing.
In adults,
this
diminished
renal
function
may
account
for about
20%
of the
observed
rise
in serum
bilirubin level with starvation.7 Phototherapy was
not
associated
with
lower
serum
bilirubin
levels
in
infants
who
received
fluids
in amounts
less
than
60
mL/kg/24
h, but
was
associated
with
lower
serum
bilirubin
levels
when
fluid
intake
was
in excess
of
this amount.
The
water-soluble
bilirubin
products
resulting
from
phototherapy
may
also
be
excreted
in
the
urine.40
Limited
fluid
intake
alone
cannot
account
for
the
decreased
efficiency
of
photother-apy
because
these
infants
are
more
likely
to
have
limited
caloric
intake
as well.
The
data
from
our
present
study,
suggesting
that
an
inverse
relation
exists
between
caloric
intake
and
serum
bilirubin
concentration
in
control
in-fants, support previous observations
on the
role
of
caloric
intake
on lowering
serum
bilirubin.*
The
mechanisms
of
the
association
of
higher
bilirubin
levels
with
fasting
are
unclear.
Increased
bilirubin
production
and
decreased
hepatic
biliru-bin
clearance
have
been
suggested
as possibilities.
Earlier
studies565
indicated
that
fasting
or
insulin-induced
hypoglycemia
produced
a marked
increase
in
the
activity
of
heme
oxygenase,
producing
an
increase
in hepatic
heme
turnover
and
leading
to
increased
bilirubin
production.
However,
studies
in
animals’2
and
newborn
infants,94
using
the
excre-tion
rate
of endogenously
produced
carbon
mon-oxide
as an
index
of bilirubin
production,
failed
to
demonstrate
any
increase
due
to
caloric
depriva-tion.
Studies
by
Bloomer
et
al’2
suggest
that
hepatic
bilirubin
clearance
may
be decreased
during
fasting.
Further,
the
rise
in level
of nonesterified
fatty
acid
(NEFA)
associated
with
fasting
may
play
an
im-portant
role
in
this
process.
The
elevated
NEFA
level
may
act
through
several
mechanisms:
(1)
NEFA
may
interfere
with
receptors
on the
hepatic
cell
membrane
that
interact
with
the
albumin
mol-ecule
to
separate
bilirubin,
and
thereby
diminish
hepatic
bilirubin
uptake.’3
Because
NEFA
com-petes
with
unconjugated
bilirubin
for
binding
by
the
Y-protein
(ligandin)
and
Z-protein
in the
cyto-plasm
of
liver
cells,29’59’7’
the
increase
in
NEFA
during
caloric
deprivation
may,
therefore,
interfere
with
intracellular
transport.
(3)
NEFA
may
de-crease
hepatic
bilirubin
clearance
by inhibiting
ur-idine
diphosphate
(UDP)-glucuronyl
transferase
activity.
This
has
been
demonstrated
in vitro”
and
in vivo
in starved
rats.77
Additionally,
Felsher
and
Carpio27
reported
that
patients
with
the
Gilbert
syndrome
and
reduced
hepatic
UDP-glucuronyl
transferase
activity
showed
a greater
increase
in
total
bilirubin
during
caloric
restriction
than
do
normal
subjects.
Thus,
there
are
several
mecha-nisms
through
which
NEFA
may
increase
uncon-jugated
serum
bilirubin
level
during
caloric
depri-vation
or restriction.
Another
mechanism
for
the
increase
in
serum
bilirubin
levels
during
restriction
of
oral
caloric
intake
may
be related
to the
enterohepatic
shunting
of bilirubin.’#{176}#{176}
Studies
by Wu
et al’#{176}7
showed
that
early
caloric
intake
facilitated
early
passage
of
me-conium, with resultant
decrease
of
absorption
of
bilirubin
back
into
circulation.
Studies
by Gartner
and
Lee32in adult
rats
indicated
that
caloric
dep-rivation
without
thirsting
markedly
increased
in-testinal
absorption
of unconjugated
bilirubin.
This
effect
was
reversed
by intravenous
glucose
admin-istration.32
These
investigators
have
also
found
that
certain
nonesterified
fatty
acids
administered
intra-duodenally
inhibit
intestinal
absorption
of bilirubin
whereas
others
increase
it, suggesting
that
different
fat
blends
in formulas
may
promote
or retard
the
reabsorption
of bilirubin.
Thus,
caloric
intake
may
alter
the
level
of
serum
bilirubin
through
both
systemic
and
enteric
pathways.
It is now
thought
that
phototherapy
causes
pho-tochemical
excitation
of
bilirubin
which
decays
back
to bilirubin,
or after
isomerization,
to
geomet-nc
isomers
of
bilirubin.
These
isomers
migrate
through
the
plasma
membrane
into
the
blood;
the
isomers
then
become
bound
to
albumin
and
are
extracted
from
blood
into
hepatocytes.#{176}’61’’69’70’95
Even
though
the
bilirubin
conjugating
system
may
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not
be functioning
adequately
during
the
first
few
days
of life,
the
more
polar
water-solvated
photo-isomers,
which
do
not
require
conjugation
for
ex-cretion,
will
be excreted
in the
bile.
In addition
to
being
more
polar
and
more
hydrophilic
than
the
natural
bilirubin,6’
the
photoisomers
are
thermo-dynamically
less
stable
than
bilirubin
and
revert
readily
to bilirubin
when
warmed
or irradiated
in
solution.6’
This
reversion
phenomenon
has
clinical
relevance
in view
of previous
reports
that
the
re-version
product,
bilirubin,
and
its
isomers,
cause
decreased
intestinal
transit
time,”#{176} decreased
nu-trient
and
water
absorption,75”#{176}and
loose
stools
by
inhibiting
intestinal
lactase.4’’89
The
tendency
ob-served
in
this
study
for
infants
receiving
photo-therapy
to have
more
frequent
stools
supports
the
findings
in previous
studies,
and
may
be explained
by the
presence
of bilirubin
isomers
in the
intestine
in the
light-treated
infants.
Additionally,
the
bili-rubin
isomers
might
be
reabsorbed
into
the
circu-lation
from
the
intestine,
which
would
reduce
the
overall
efficiency
of its removal.
Higher
oral
caloric
feeding,
by
promoting
peristaltic
movements
and
early
passage
of stools,’#{176}7would
tend
to remove
the
bilirubin
and
its
isomers
and
decrease
their
reab-sorption,
thus
increasing
the
efficiency
of
photo-therapy.
The
factors
discussed
above
would
appear
to be
most
evident
in infants
in
group
1. In
infants
in
groups
2 and
3, the
association
of these
factors
with
lowering
of bilirubin
level
is less
evident.
This
may
be partly
due
to the
design
of the
protocol.
In the
groups
of infants
with
greater
weight,
many
of the
infants
entered
the
study
after
their
serum
bilirubin
level
had
peaked.
In
addition,
their
conjugation
system
would
be
more
mature
and
function
more
adequately.
These
two
factors
would
tend
to
hide
some
of the
overt
association
between
caloric
intake
and
bilirubin
levels
observed
in infants
in group
1.
CONCLUSION
The
influence
of fluid
and
caloric
intake
on
neo-natal
jaundice
and
efficacy
of
phototherapy
was
evaluated.
Results
indicate
that
overall,
higher
fluid
and
caloric
intake
were
associated
with
lower
daily
mean
serum
bilirubin
level
in both
phototherapy-treated
and
control
infants.
This
association
was
stronger
with
increased
calories
than
with
increased
fluids,
and
primarily
was
dependent
on oral
caloric
intake.
The
inverse
correlation
between
oral
caloric
intake
and
serum
bilirubin
level
was
more
marked
in infants
in the
lowest
birth
weight
group
(< 2,000
g) in which
phototherapy
was
used
to prevent
hy-perbilirubinemia.
The
caloric
effect
was
less evident
in
infants
in
the
higher
birth
weight
groups
and
when
phototherapy
was
used
to
treat
established
hyperbilirubinemia.
SUPPLEMENT
439
used
in
the
clinical
trial
of phototherapy
demon-
considered
reliable.
Problems
such
as
these
must
strated
potential
for
efficiently
obtaining
light
ex-
be resolved
before
the
photodosimeter
system
could
posure
data
integrated
over
time
for a large
number
reach
widespread
clinical
usefulness.
of
infants.
However,
because
of variation
in
per-formance
of the
badge
and
probable
deterioration
in
some
badges
over
time,
the
system
cannot
yet
be
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